Studies are proposed in four areas of cellular and molecular immunology. 1. Studies on a T helper stimulatory factor, THSF, a new lymphokine described by us in the previous grant period. THSF is derived from a cloned thymic epithelial cell line and appears to act on peripheral L3T4 T cells to coinduce the synthesis of lL2. (a) The factor will be purified to homogeneity and the cDNA coding for THSF will be identified and sequenced. (b) The purified factor will be used in receptor ligand studies. (c) A biological study will be carried out to determine the number of cell types upon which THSF acts and the precise nature of its effect. 2. Two lines of analysis are proposed to investigate the nature of T cell-B cell interactions, one, direct visualization studies with living stained cells, two, an analysis of T cell-B cell interactions in B cell differentiation. 3. Studies on the role antigen in the differentiation phase of the B cell response analysed with cells from transgenic mice expressing rearranged immunoglobulin genes with cells expressing the V-ese gene in the B cell response to High-SRBC. 4. The development of an experimental model to investigate the role of T cells and T cell products in the regulation of B cells isotypes.